Clinical Trials

The main purposes of a clinical trial are as follows.

A nonclinical study is a phase carried out before clinical trials involving human subjects.

In this phase, it is confirmed whether the developed candidate substance or medical device prototype has a level of safety and basic efficacy suitable for application in the human body.

Such nonclinical studies also include a process that evaluates safety and the mechanism of action using not only animal testing but also various alternative test methods, such as organoid-based tests that replicate the structure and function of human tissue.

For a pharmaceutical developer to conduct a clinical trial, it must submit an IND (Investigational New Drug application) to the Ministry of Food and Drug Safety (MFDS).

The IND application must include detailed information on the clinical trial plan and on the safety of the investigational medicinal product (IMPD).

To submit an IND, a pharmaceutical company must prepare materials such as the following.

The Ministry of Food and Drug Safety reviews the submitted materials and then decides whether to approve the clinical trial.

In addition, if a sponsor wishes to change the trial during its course in a way that differs from the previously approved IND, it must meet the requirements again and apply for approval of the IND change.

For example, this includes a change of the active-ingredient manufacturer, changes to the investigational medicinal product, and increases or decreases in dose.

A Phase 1 clinical trial is conducted in healthy volunteers, on a scale ranging from a few to several dozen people.

In this phase, the focus is on evaluating safety, including the absorption, distribution, metabolism, and excretion of the new drug or medical device within the body, along with the presence of any adverse reactions.

A Phase 2 clinical trial is conducted in a small number of patients who have the relevant disease, generally on a scale ranging from several dozen to several hundred people.

In this phase, the appropriate dosage and dosing regimen of the new drug or medical device are set, and efficacy and the possibility of indication are evaluated against the actual disease.

A Phase 3 clinical trial is conducted with a large number of target patients, ranging from several hundred to several thousand participants.

At this stage, the safety and efficacy of the new drug or medical device are confirmed on a larger scale, and the efficacy, effects, dosage and administration, and precautions for use are set out in specific terms.

Once a clinical trial is completed, an application for product approval is filed with the MFDS or an overseas regulatory agency based on the safety and efficacy data obtained.

For a new drug, the following materials must be submitted, while for drugs requiring data submission, only the necessary safety and efficacy data are selected and submitted from among these.

For generic drugs, bioequivalence test data and quality data are submitted in place of toxicity and clinical data to demonstrate equivalence to the reference drug.

During the review process, a GMP conformity assessment, a review of patent relations, and, if necessary, consultation with the Central Pharmaceutical Affairs Council are carried out together, and final product approval is granted when all requirements are met.

As major regulatory bodies, including the U.S. FDA, have begun to gradually reform the existing nonclinical evaluation system centered on animal testing, alternative test methods (NAMs), including organoids, are establishing themselves as a core element of new drug development strategy.

This is not merely a change in research methods, but a development that is bringing substantial changes to the way IND approval materials are composed and to the overall standards for nonclinical data requirements.

Organoid-based data supplement existing animal testing materials and are used in the IND approval process.

This allows for setting the safety range of a drug and estimating the initial dose, and it also serves as an important basis for judgment in the early stage of clinical trial design.

Accordingly, pharmaceutical companies and research institutions are increasingly taking a strategic approach to reviewing whether to use organoids from the clinical trial protocol design stage.

Organoids have the strength of being able to partially reproduce the structure and function of actual human organs, but technical limitations still remain in fully implementing complex physiological environments such as the vascular system, the immune system, and the microbial environment.

To compensate for these limitations, a combined preclinical strategy is being applied that uses multi-organoid systems connecting multiple organ organoids together with AI-based drug response prediction models in parallel.